8/9/2023 0 Comments Tissue antibody repertoirec | Maturation and development of a potent adaptive response continues in lymph nodes downstream of the vaccination site (draining lymph nodes). Soluble vaccine components and activated cells enter the lymphatics and travel to local lymph nodes. As innate immune cells become activated, they release cytokines that attract other immune cells from the bloodstream to the site of administration. The antigen component of the vaccine is endocytosed and broken down by APCs before being presented on the APC surface major histocompatibility complex (MHC) molecules. At the site of administration, innate immune cells, such as neutrophils and antigen-presenting cells (APCs), first encounter the antigen and adjuvant. b | Following administration of a vaccine, interactions between cells and vaccine components lead to a strong and lasting response. In this Review, we highlight the biological mechanisms underlying strong humoral and cell-mediated immune responses and explore materials design strategies to manipulate and control these mechanisms.Ī | Timeline of major events in drug delivery and vaccine development. Materials-based vaccination strategies can augment the immune response by improving innate immune cell activation, creating local inflammatory niches, targeting lymph node delivery and controlling the time frame of vaccine delivery, with the goal of inducing enhanced memory immunity to protect against future infections. Material platforms, such as nanoparticles, hydrogels and microneedles, can be engineered to spatially and temporally control the interactions of vaccine components with immune cells. As our knowledge of the immune system deepens, it becomes clear that vaccine components must be in the right place at the right time to orchestrate a potent and durable response. However, increasing the potency, quality and durability of the vaccine response remains a challenge. ©2021 American Association for Cancer Research.Vaccines are the key technology to combat existing and emerging infectious diseases. Our findings propose beneficial remodeling of the TCR repertoire following transient CD4 + cell depletion and provide novel insight into the antitumor effects of monoclonal anti-CD4 treatment in patients with cancer. These results suggested that the clonal replacement of the TCR repertoire induced by transient CD4 + cell depletion was accompanied by the expansion of tumor-reactive T-cell clones that mediated antitumor responses. The greater expansion of CD8 + overlapping clones was commonly observed in the patients who achieved tumor shrinkage. The total frequency of blood-tumor overlapping clones tended to increase in patients receiving a depleting dose of anti-CD4, which was accompanied by the replacement of overlapping clones. Next, we focused on T-cell clones overlapping between the blood and tumor in order to track tumor-associated T-cell clones in the blood. This replacement of the TCR repertoire was associated with the extent of CD4 + T-cell depletion and an increase in CD8 + T-cell count in the blood. Transient depletion of CD4 + cells promoted replacement of T-cell clones among CD4 + and CD8 + T cells in the blood. To investigate the clonal T-cell responses following transient CD4 + cell depletion in patients with cancer, we conducted a temporal analysis of the T-cell receptor (TCR) repertoire in the first-in-human clinical trial of IT1208, a defucosylated humanized monoclonal anti-CD4. 10 Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan.Īntibody-mediated transient depletion of CD4 + cells enhances the expansion of tumor-reactive CD8 + T cells and exhibits robust antitumor effects in preclinical and clinical studies.9 IDAC Theranostics, Inc., Tokyo, Japan.8 Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.7 Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.6 Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.5 Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.4 Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 3 Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.2 Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Tokyo, Japan.1 Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |